The objective of this study is to delineate the molecular nature of an functional roles of Reticulum Cell Sarcoma (RCS) tumor-associated antigens involved in triggering syngeneic host lymphocytes. Preliminary findings from our laboratory have shown that RCS tumor cells express IE/C hybrid antigens which are not expressed on the host cells. In addition, Ia antigen expression on RCS tumor cells has been shown to be involved in syngeneic proliferation. This proposal will investigate the role played by Ia antigens on RCS tumor cells in the syngeneic mixed leukocyte tumor interaction (MLTI). Genetic mapping of the antigens involved in stimulation and recognition by the antitumor effector cell will be determined by appropriate strains of mice and the use of antibody blocking reagents. In additions, the requirements for cellular interactions in syngeneic MLTI will be determined and compared to the Mixed Leukocyte Reaction. The role of RCS Ia antigens in the induction of interleukins (IL-2) and the role played by IL-2 in MLTI will be determined also. Preliminary findings have shown that the syngenetic effector cells in MLTI suppress MLTI responses by normal cells. These suppressor cells and their derived suppressor factors will be examined, as well as their role in regulating tumor growth in vivo. The above studies will make use of primary spontaneous and transplantable tumors, monoclonal antibody reagents, and TCGF-dependent anti-tumor T cell lines. The studies proposed will correlate the in vitro findings with the in vivo effects. The expression of well defined Ia antigens on RCS tumors which are absent in normal host cells provides a good model system for studying host-tumor interactions.